Differences In Pathophysiology Research Articles

Cardiogenic shock-sex-specific risk factors and outcome differences.

Cardiogenic shock (CS) remains a high-mortality condition despite technological and therapeutic advances. One key to potentially improving CS prognosis is understanding patient heterogeneity and which patients may benefit most from different treatment options, a key element of which is sex differences. While cardiovascular diseases (CVDs) have historically been considered a male-dominant condition, the field is increasingly aware that females are also a substantial portion of the patient population. While estrogen has been implicated in protective roles against CVD and tissue hypoxia, its role in CS remains unclear. Clinically, female CS patients tend to be older, have more severe comorbidities and are more likely to have non-acute myocardial infarction etiologies with preserved ejection fractions. Female CS patients are more likely to receive pharmacotherapy while less likely to receive mechanical circulatory support. There is increased short-term mortality in females, although long-term mortality is similar between the sexes. More sex-specific and age-stratified research needs to be done to fully understand the relevant pathophysiological differences in CS, to better recognize and manage CS patients and reduce its mortality.

Differences in Pathophysiology and Treatment Efficacy Based on Heterogeneous Out-of-Hospital Cardiac Arrest.

Out-of-hospital cardiac arrest (OHCA) is heterogeneous in terms of etiology and severity. Owing to this heterogeneity, differences in outcome and treatment efficacy have been reported from case to case; however, few reviews have focused on the heterogeneity of OHCA. We conducted a literature review to identify differences in the prognosis and treatment efficacy in terms of CA-related waveforms (shockable or non-shockable), age (adult or pediatric), and post-CA syndrome severity and to determine the preferred treatment for patients with OHCA to improve outcomes.

Comparison of β-Cell Function and Insulin Sensitivity Between Normal-Weight and Obese Chinese With Young-Onset Type 2 Diabetes.

Normal-weight individuals with usual-onset type 2 diabetes had reduced beta-cell function and greater insulin sensitivity compared to their obese counterparts. The relative contribution of beta-cell dysfunction and insulin resistance to young-onset type 2 diabetes (YOD) among normal-weight individuals is not well established. In 44 individuals with YOD (24 normal-weight and 20 obese) and 24 healthy controls with normoglycemia (12 normal-weight and 12 obese), we conducted 2-h 12mmol/L hyperglycemic clamps to measure acute (0-10 minute) and steady-state (100-120 minute) insulin and C-peptide responses, and insulin sensitivity index. Normal-weight individuals with YOD had lower acute insulin response, steady-state insulin and C-peptide responses, and higher insulin sensitivity index compared to their obese counterparts with YOD. When compared to BMI-matched healthy controls, normal-weight individuals with YOD had lower acute and steady-state insulin and C-peptide responses but similar insulin sensitivity index. The impairment of steady-state beta-cell response relative to healthy controls was more pronounced in normal-weight versus obese individuals with YOD. In conclusion, normal-weight Chinese with YOD exhibited worse beta-cell function but preserved insulin sensitivity relative to obese individuals with YOD and BMI-matched healthy individuals with normoglycemia. The selection of glucose-lowering therapy should account for pathophysiological differences underlying YOD between normal-weight and obese individuals.

A Comparative Review of Typical and Atypical Optic Neuritis: Advancements in Treatments, Diagnostics, and Prognosis.

Optic neuritis (ON) is a debilitating condition thatthrough various mechanisms, including inflammation or demyelination of the optic nerve, can result in partial or total permanent vision loss if left untreated. Accurate diagnosis and promptly initiated treatment are imperative related to the potential of permanent loss of vision if left untreated, which can lead to a significant reduction in the quality of life in affected patients. ONis subtyped as "typical" or "atypical" based on underlying causative etiology. The etiology of ON can be differentiated when appropriate diagnostic testing is performed. Using history taking, neuroimaging, and visual testing to localize the underlying pathology of ON in a time-sensitive manner is critical in mitigating these unsatisfactory outcomes. Herein, we examine the differences in presentation, pathophysiology, and treatments of typical ON causes, like multiple sclerosis (MS), and atypical causes such as neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein (MOG)-immunoglobulin G (IgG) ON. The present investigation places focus on both neuroimaging and visual imaging in the differentiation of ON. Additionally, this review presents physicians with a better understanding of different presentations, treatments, and prognoses of ON.

Impact of biological sex on valvular heart disease, interventions, and outcomes.

Valvular heart disease (VHD) is common, affecting>14% of individuals aged >75, and is associated with morbidity, including heart failure and arrhythmia, and risk of early mortality. Increasingly, important sex differences are being found between males and females with VHD. These sex differences can involve the epidemiology, pathophysiology, presentation, diagnosis, and outcomes of the disease. Females are often disadvantaged, and female sex has been shown to be associated with delayed diagnosis and inferior outcomes in various forms of VHD. In addition, the unique pathophysiologic state of pregnancy is associated with increased risk for maternal and fetal morbidity and mortality in many forms of VHD. Therefore, understanding and recognizing these sex differences, and familiarity with the attendant risks of pregnancy and management of pregnant females with VHD, is of great importance for any primary care or cardiovascular medicine practitioner caring for the female patient. This review will outline sex differences in aortic, mitral, pulmonic, and tricuspid VHD, with particular focus on differences in pathophysiology, clinical presentation, and outcomes. In addition, the pathophysiology and management implications of pregnancy will be discussed.

Mid-pregnancy allopregnanolone levels and trajectories of perinatal depressive symptoms

Perinatal depression is a major cause of disability for individuals giving birth worldwide, with detrimental effects on short- and long-term parental and child outcomes. There is emerging evidence that the neuroactive steroid hormone allopregnanolone is implicated in the pathophysiology and course of perinatal mood symptoms. However, no study thus far has examined allopregnanolone levels whilst making use of longitudinal data on depressive symptom trajectories throughout the perinatal period. The present study investigated levels of allopregnanolone at gestational week 17 of 252 participants in relation to perinatal depressive symptom trajectories, with a secondary aim of exploring the role of history of depression as an effect modifier. Four perinatal depressive symptom trajectories were investigated: controls (no depressive symptoms throughout perinatal period) (N=161), antepartum (depressive symptoms prenatally with postpartum remission) (N=31), postpartum-onset (no depressive symptoms during pregnancy, development of depressive symptoms postpartum) (N=23), and persistent (depressive symptoms throughout the perinatal period) (N=37). Results show that for every one nmol/l increase in allopregnanolone, there was 7% higher odds for persistent depressive symptoms (OR 1.07, 95% CI 1.01–1.14) compared to controls. No association was seen for antepartum and postpartum-onset depressive symptoms. History of depression did not modify the association between allopregnanolone and perinatal depressive symptom trajectories. These results show the role of allopregnanolone for persistent depressive symptoms and strengthen the hypothesis of differences in pathophysiology among the trajectories.

Right Heart Remodeling and Outcomes in Patients With Tricuspid Regurgitation: A Literature Review and Meta-Analysis

BackgroundFunctional tricuspid regurgitation (TR) can develop either because of right ventricular (RV) remodeling (ventricular functional TR) and/or right atrial dilation (atrial functional TR). ObjectivesThis meta-analysis aimed to investigate the association between right heart remodeling and long-term (>1 year) all-cause mortality in patients with significant TR (at least moderate, ≥2+). MethodsMEDLINE, ISI Web of Science, and SCOPUS databases were searched. Studies reporting data on at least 1 RV functional parameter and long-term all-cause mortality in patients with significant TR were included. This study was designed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) requirements. ResultsOut of 8,902 studies, a total of 14 were included, enrolling 4,394 subjects. The duration of follow-up across the studies varied, ranging from a minimum of 15.5 months to a maximum of 73.2 months. Overall, long-term all-cause mortality was 31% (95% CI: 20%-41%; P ≤ 0.001). By means of meta-regression analyses, an inverse relation was found between tricuspid annular plane systolic excursion (11 studies enrolling 3,551 subjects, −6.3% [95% CI: −11.1% to −1.4%]; P = 0.011), RV fractional area change (9 studies, 2,975 subjects, −4.4% [95% CI: −5.9% to −2.9%]; P < 0.001), tricuspid annular dimension (7 studies, 2,986 subjects, −4.1% [95% CI: −7.6% to −0.5%]; P = 0.026), right atrial area (6 studies, 1,920 subjects, −1.9% [95% CI: −2.5% to −1.3%]; P < 0.001) and mortality. ConclusionsRV dysfunction parameters are associated to worse clinical outcomes in patients with TR, whereas right atrial dilatation is linked to a better prognostic outcome. Further studies are needed to unravel the pathophysiological differences within the functional TR spectrum. (Right heart remodeling and outcomes in patients with tricuspid regurgitation; CRD42023418667)

Gender Differences in Adults With Chronic Rhinosinusitis: A Scoping Review.

Gender differences in chronic rhinosinusitis (CRS) have been demonstrated in many studies over the last 15 years. The purpose of this scoping review is to investigate the current knowledge on gender differences in CRS and to analyze the gaps in the literature. A systematic search of PubMed, Cochrane Library, and Embase databases was performed. This scoping review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines. Studies that evaluated gender differences in CRS were included in the review. Of the 523 abstracts reviewed, a total of 23 studies met the criteria for inclusion. Articles consisted of retrospective and prospective cohort studies. They were divided into 3 categories based on whether they evaluated gender differences in (1) presentation and baseline quality of life, (2) pathophysiology, and/or (3) outcomes of treatment. Eleven studies addressed differences in presentation, 5 addressed differences in pathophysiology, and 10 dealt with differences in outcomes after surgical or medical management. Most of the studies showed worse baseline QoL secondary to CRS in women, with outcome of treatment being similar in both genders. The experience of CRS appears to vary between genders, with women experiencing a greater subjective burden of disease than men, though with similar outcomes after treatment. Further research is indicated, particularly involving the pathophysiology of CRS, to fully understand the underlying causes of these discrepancies.

Distinguishing heart failure with reduced ejection fraction from heart failure with preserved ejection fraction: A phenomics approach.

Pathophysiological differences between patients with heart failure with preserved (HFpEF) and reduced (HFrEF) ejection fraction (EF) remain unclear. Therefore we used a phenomics approach, integrating selected proteomics data with patient characteristics and cardiac structural and functional parameters, to get insight into differential pathophysiological mechanisms and identify potential treatment targets. We report data from a representative subcohort of the prospective Singapore Heart Failure Outcomes and Phenotypes (SHOP), including patients with HFrEF (EF <40%, n = 217), HFpEF (EF ≥50%, n = 213), and age- and sex-matched controls without HF (n = 216). We measured 92 biomarkers using a proximity extension assay and assessed cardiac structure and function in all participants using echocardiography. We used multi-block projection to latent structure analysis to integrate clinical, echocardiographic, and biomarker variables. Candidate biomarker targets were cross-referenced with small-molecule and drug databases. The total cohort had a median age of 65 years (interquartile range 60-71), and 50% were women. Protein profiles strongly discriminated patients with HFrEF (area under the curve [AUC] = 0.89) and HFpEF (AUC = 0.94) from controls. Phenomics analyses identified unique druggable inflammatory markers in HFpEF from the tumour necrosis factor receptor superfamily (TNFRSF), which were positively associated with hypertension, diabetes, and increased posterior and relative wall thickness. In HFrEF, interleukin (IL)-8 and IL-6 were possible targets related to lower EF and worsening renal function. We identified pathophysiological mechanisms related to increased cardiac wall thickness parameters and potentially druggable inflammatory markers from the TNFRSF in HFpEF.

Validation of Distinct Bladder Pain Phenotypes Utilizing the MAPP Research Network Cohort

Introduction and HypothesisAs interstitial cystitis/bladder pain syndrome (IC/BPS) likely represents multiple pathophysiologies, we sought to validate three clinical phenotypes of IC/BPS patients in a large, multi-center cohort using unsupervised machine learning (ML) analysis.MethodsUsing the female Genitourinary Pain Index and O’Leary-Sant Indices, k-means unsupervised clustering was utilized to define symptomatic phenotypes in 130 premenopausal IC/BPS participants recruited through the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) research network. Patient-reported symptoms were directly compared between MAPP ML-derived phenotypic clusters to previously defined phenotypes from a single center (SC) cohort.ResultsUnsupervised ML categorized IC/BPS participants into three phenotypes with distinct pain and urinary symptom patterns: myofascial pain, non-urologic pelvic pain, and bladder-specific pain. Defining characteristics included presence of myofascial pain or trigger points on examination for myofascial pain patients (p = 0.003) and bladder pain/burning for bladder-specific pain patients (p < 0.001). The three phenotypes were derived using only 11 features (fGUPI subscales and ICSI/ICPI items), in contrast to 49 items required previously. Despite substantial reduction in classification features, unsupervised ML independently generated similar symptomatic clusters in the MAPP cohort with equivalent symptomatic patterns and physical examination findings as the SC cohort.ConclusionsThe reproducible identification of IC/BPS phenotypes, distinguishing bladder-specific pain from myofascial and genital pain, using independent ML analysis of a multicenter database suggests these phenotypes reflect true pathophysiologic differences in IC/BPS patients.

P307 Novel proteomic analysis of 11,000 serum proteins distinguishes between Crohn’s disease and ulcerative colitis in pediatric patients

Abstract Background While the two main inflammatory bowel diseases (IBD), Crohn’s disease (CD) and ulcerative colitis (UC), share various clinical features, they differ in clinical, endoscopic and histological features, and may have different underlying etiopathological mechanisms, resulting in different treatment options. Consequently, the development of reliable, highly accurate, non-invasive biomarkers that differentiate CD and UC in pediatric IBD are an unmet need of paramount importance in terms of medical care, surgical intervention, and prognosis. The most advanced proteomics technology, the aptamer-based SomaScan, enables measurement of 11,000 biologically relevant proteins, including very low abundant proteins, and was tested to discover serum protein biomarkers capable of differentiating between pediatric CD and UC. Methods SomaScan (SomaLogic; Boulder, CO) quantitative serum protein profiles were generated from pediatric subjects diagnosed with CD (n=56) and UC (n=25) using standard diagnostic criteria. The disease location for patients with CD was 18 L1 (ileal), 9 L2 (colonic), 27 L3 (ileo-colonic) and 2 L4 (small bowel); Inflammatory phenotype (B1) occurred in 40, stricturing (B2) in 8, penetrating (B3) in 6, and B2B3 in 2. To develop highaccuracy predictors with the lowest number of proteins for discriminating CD from UC, we used machine learning and conditional logistic regression to calculate odds ratios(OR) and 95% confidence intervals(CI) per one standard deviation increase in protein levels. Area under the curve (AUC) was calculated to determine the performance of the multi-protein model in discriminating CD cases from UC cases. Ingenuity pathway analysis was conducted to identify pathophysiological pathway differences between CD and UC. Results There were 256 proteins that were discriminating between CD and UC with fold change &amp;gt;1.3 and an unadjusted p-value &amp;lt;0.05. Of these, 38 proteins were associated with increased odds and 218 proteins were associated with decreased odds of CD diagnosis. Compared to UC, CD cases had decreased neutrophil movement and degranulation, inflammatory response, and metabolism of reactive oxygen species but enhanced apoptosis. When we developed a multi-protein model and assessed its performance to discriminate CDs cases from UC cases, a 4-protein model showed an AUC=0.97. Conclusion Using the most comprehensive proteomics platform, we identified serum proteins and developed a high accuracy multi-protein model discriminating between pediatric CD and UC. The utility of SomaScan demonstrates not only the value of these diagnostic biomarkers, but also the potential to discover immune and metabolic pathways that distinguish CD from UC.

DOP27 Systemic antibody responses against gut microbiota flagellins implicate shared and divergent immune reactivity in Crohn's Disease and chronic fatigue syndrome

Abstract Background Patients with Crohn’s disease (CD) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) exhibit elevated antibody responses against gut microbiota flagellins. However, flagellin-specific antibody repertoires and functional roles in the diseases remain incompletely understood. Bacterial flagellins can be categorized into three types depending on their interaction with toll-like receptor 5 (TLR5): (1) "stimulator" and (2) "silent" flagellins, binding TLR5 through a conserved N-terminal motif, with only stimulators activating TLR5 due to a specific C-terminal domain; (3) "evader" flagellins of pathogens, which circumvent TLR5 activation via mutated N-terminal TLR5 binding motifs. Here we studied the characteristics, epitope binding, and sequence (dis)similarity of anti-flagellin antibody responses in CD and ME/CFS. Methods Since conventional antibody profiling methods like enzyme-linked immunosorbent assays [ELISAs] do not allow for large-scale measurements of antibody repertoires, we leveraged phage-display immunoprecipitation sequencing (PhIP-Seq) to characterize 344,000 rationally selected peptide antigens in 256 patients with CD, 40 patients with ME/CFS and in two equally sized groups of age- and sex-matched healthy controls from population-based cohorts in the Netherlands and U.K., respectively. Different sequence alignment strategies were employed to compare flagellin peptide structures with observed antibody-bound flagellin peptide reactivity. Results Both patients with CD and ME/CFS exhibited elevated antibody responses against distinct regions of flagellin peptides compared to healthy individuals (P&amp;lt;0.001). N-terminal binding to Lachnospiraceae flagellins was comparable in both diseases, while C-terminal binding was more prevalent in CD. N-terminal antibody-bound flagellin sequences were similar across CD and ME/CFS, resembling ‘stimulator’ and ‘silent’ flagellins more than evaders. However, C-terminal antibody-bound flagellins showed higher resemblance to stimulator than to silent flagellins in CD, but not in ME/CFS. This group of antibody-bound flagellins was exclusively identified in a subset (10-20%) of patients with CD and characterized by its strong overrepresentation (exceeding 20-fold), underscoring its potential significance in distinguishing pathophysiologic subtypes of CD. Conclusion Antibody binding to the N-terminal domain of stimulator and silent flagellins may impact TLR5 activation in both CD and ME/CFS patients. Furthermore, elevated antibody binding to the C-terminal domain of stimulator flagellins in CD may explain pathophysiological differences between diseases. Our results highlight the diagnostic potential of these antibody responses and their impact on innate/adaptive immunity balance.

Clinical and molecular characterization of patients with hereditary hemorrhagic telangiectasia from two different regions of Brazil

Hereditary hemorrhagic telangiectasia (HHT) is a vascular dysplasia characterized hemorrhagic diseases described in consensus clinical diagnostic criteria (Curaçao). We describe the clinical and molecular characteristics of HHT patients from two different geographic regions of Brazil (São Paulo and Manaus). Demographic and clinical data were obtained from the electronic medical records and molecular analysis was performed by Sanger sequencing. We present here the first clinical characterization concomitantly with a molecular study of patients with THH in Brazil. These clinical characterizations may reveal differences in the molecular pathophysiology of HHT in Brazil - that our phenotypic database opens the way to be studied, or indicate limitations in the care of these patients, who need a multidisciplinary attention to prevent and treat the complications of this condition. Our results, combined with our previous data with patients presenting mutation rate to 93,75% (n=15/16) in Brazilians patients with a confirmed clinical diagnosis. Also emphasize the higher numbers of intronic mutations and three large deletions 5ÙTR regions and the predominance of ACVRL1 over ENG mutations.

Differences in left ventricular myocardial function and infarct size in female patients with ST elevation myocardial infarction and spontaneous coronary artery dissection.

Differences in pathophysiology, clinical presentation, and natural course of ST-elevation myocardial infarction in female patients due to either spontaneous dissection (SCAD-STEMI) or atherothrombotic occlusion (type 1 STEMI) have been discussed. Current knowledge on differences in left ventricular myocardial function and infarct size is limited. The aim of this study was to assess baseline clinical characteristics, imaging findings, and therapeutic approach and to compare differences in echocardiographic findings at baseline and 3-month follow-up in patients with SCAD-STEMI and type 1 STEMI. This was a prospective multicenter study of 32 female patients (18-55 years of age) presenting with either SCAD-STEMI due to left anterior descending coronary artery (LAD) dissection or type 1 STEMI due to atherothrombotic LAD occlusion. The two groups were similar in age, risk factors, comorbidities, and complications. SCAD-STEMI patients more often had Thrombolysis in Myocardial Infarction 3 flow, while type 1 STEMI patients were more often treated with percutaneous coronary intervention and dual antiplatelet therapy. Baseline mean left ventricular (LV) ejection fraction (LVEF) was similar in the two groups (48.0% vs. 48.6%, p = 0.881), but there was a significant difference at the 3-month follow-up, driven by an improvement in LVEF in SCAD-STEMI compared to type 1 STEMI patients (Δ LVEF 10.1 ± 5.3% vs. 1.8 ± 5.1%, p = 0.002). LV global longitudinal strain was slightly improved in both groups at follow-up; however, the improvement was not significantly different between groups (-4.6 ± 2.9% vs. -2.0 ± 2.8%, p = 0.055). The results suggest that female patients with SCAD-STEMI are more likely to experience improvement in LV systolic function than type 1 STEMI patients.

Anterior-wall and non-anterior-wall STEMIs do not differ in long-term mortality: results from the augsburg myocardial infarction registry.

Different ST-segment elevation myocardial infarction (STEMI) localizations go along with dissimilarities in the size of the affected myocardium, the causing coronary vessel occlusion, and the right ventricular participation. Therefore, this study aims to clarify if there is any difference in long-term survival between anterior- and non-anterior-wall STEMI. This study included 2,195 incident STEMI cases that occurred between 2009 and 2017, recorded by the population-based Augsburg Myocardial Infarction Registry, Germany. The study population comprised 1.570 men and 625 women aged 25-84 years at acute myocardial infarction. The patients were observed from the day of their first acute event with an average follow-up period of 4.3 years, (standard deviation: 3.0). Survival analyses and multivariable Cox regression analyses were performed to examine the association between infarction localizations and long-term all-cause mortality. Of the 2,195 patients, 1,118 had an anterior (AWS)- and 1,077 a non-anterior-wall-STEMI (NAWS). No significant associations of the STEMI localization with long-term mortality were found. When comparing AWS with NAWS, a hazard ratio of 0.91 [95% confidence interval: 0.75-1.10] could be calculated after multivariable adjustment. In contrast to NAWS, AWS was associated with a greater <28 day mortality, less current or former smoking and higher creatine kinase-myocardial band levels (CK-MB) and went along with a higher frequency of impaired left ventricular ejection fraction (<30%). Despite pathophysiological differences between AWS and NAWS, and identified differences in multiple clinical characteristics, no significant differences in long-term mortality between both groups were observed.

Comparison of pathophysiological differences in TAFRO syndrome with or without lymphadenopathy.

In diagnosing TAFRO syndrome, lymph node histology often may not be evaluated due to inapparent lymphadenopathy. In this study, we analyzed the differences in the pathophysiology of TAFRO syndrome with or without lymphadenopathy. We used an anonymous questionnaire to survey 70 hematologists at 50 hospitals in the Kanto Koshinetsu area of Japan from February to April 2020. We received 31 responses and collected 26 cases with TAFRO syndrome. Compared to cases with or without lymph node biopsy, clinical features and laboratory test findings in both groups were not significantly different, except for stronger renal insufficiency found in those without biopsy. It was also revealed that clinical features and laboratory test findings had no significant differences between the cases with and without lymphadenopathy. However, renal insufficiency was more pronounced in those without lymphadenopathy. There were no significant differences in pathophysiology between cases with or without lymphadenopathy in the group that did not undergo lymph node biopsy. In the treatment strategies, no significant differences were found dependent on lymphadenopathy. This study shows that lymphadenopathy in TAFRO syndrome may be secondary to inflammation and unrelated to the underlying disease.

Cognition and Behavior in the Aging Brain Following TBI: Surveying the Preclinical Evidence.

Elderly individuals (65years and older) represent the fastest-growing demographic of new clinical traumatic brain injury (TBI) cases, yet there is a paucity of preclinical research in aged animals. The limited preclinical work available aligns with the clinical literature in that there appear to be significant differences in pathophysiology, recovery potential, and response to medications between animals at different points across the age spectrum. The aim of this review is to discuss the limited studies and highlight critical age-related differences in affective, cognitive, and neurobehavioral deficits, to discuss factors that influence functional outcomes, and to identify targets for future research. The consensus is that aged rodents face challenges related to dysregulated inflammation, reduced neuroplasticity, and age-related cellular changes, which hinder their recovery after TBI. The most successful intervention studies in animal models to date, of the limited array available, have explored interventions targeting inflammatory downregulation. Current standards of neuropsychopharmacology for post-TBI neurocognitive recovery have not been investigated in a significant capacity. In addition, currently available animal models do not sufficiently account for important age-related comorbidities, dual insults, or differences in TBI mechanism of injury in elderly individuals. TBI in the aged population is more likely to lead to additional neurodegenerative diseases that further complicate recovery. The findings underscore the need for tailored therapeutic interventions to improve outcomes in both adult and elderly populations.

Oxidative stress in the pathogenesis of chronic headache

Given new information about the development of oxidative stress (OS) in chronic headache. The main biochemical characteristics of OS are presented. Changes in MRI and biochemical markers confirming the development of OS in migraine are described. The absence of significant differences in OS rates for migraine without aura and with aura is emphasized. The pathophysiological differences between migraine and chronic tension headache, in which OS is not detected, are shown. The possible activation of TRPA1 ion channels and CGRP peptides during OS, which provokes migraine attacks, is discussed. Directions of pathogenetic therapy OS are given.

ОСТЕОПОРОЗ ПРИ БОЛЕЗНИ КРОНА (ОБЗОР ЛИТЕРАТУРЫ)

Crohn's disease is a chronic inflammatory bowel disease of unknown etiology which is characterized not only by damage to the gastrointestinal tract, but also by various extraintestinal manifestations. One of the extraintestinal manifestations not associated with the activity of the process is osteoporosis, the etiopathogenesis of which has not been fully studied. Complications associated with osteoporosis in the form of fractures of bone structures can worsen the condition of patients, lead to disability and death among both the elderly and the young, working-age population. A decrease in bone mineral density in Crohn's disease is a known, but insufficiently studied extraintestinal complication which receives little attention from specialists in different countries, including Russia. Screening, diagnosis and treatment are currently focused mainly on individuals with idiopathic and postmenopausal osteoporosis, but these methods cannot be applied to patients with inflammatory bowel disease due to differences in age group and pathophysiology of bone loss. This review aims to highlight the currently available information on the etiology, pathogenesis, diagnosis, treatment and prevention of osteoporosis in Crohn's disease.

XVI Post-ECTRIMS Meeting: review of the new developments presented at the 2023 ECTRIMS Congress (I)

The XVI Post-ECTRIMS meeting took place in Seville on 20 and 21 October 2023. This meeting was attended by neurologists specialising in multiple sclerosis (MS) from Spain, who shared a summary of the most interesting innovations at the ECTRIMS congress, which had taken place in Milan the previous week. The aim of this article is to summarise new developments related to the pathogenesis, diagnosis and prognosis of MS. The contributions of innate immunity and central nervous system resident cells, including macrophages and microglia in MS pathophysiology and as therapeutic targets were discussed. Compartmentalised intrathecal inflammation was recognised as central to understanding the progression of MS, and the relationship between inflammatory infiltrates and disease progression was highlighted. Perspectives in demyelinating pathologies were reviewed, focusing on neuromyelitis optica and myelin oligodendrocyte glycoprotein antibody-associated disease, highlighting their pathophysiological and diagnostic differences compared to MS. Advances in neuroimaging were also discussed, and especially the analysis of active chronic lesions, such as paramagnetic rim lesions. In the absence of clinical improvements in trials of remyelinating treatments, methodological strategies to optimise the design of future studies were proposed. Breakthroughs in detecting the prodromal phase of MS, the use of biomarkers in body fluids to assess activity, progression and treatment response, and research on progression independent of flares were addressed. The need to define criteria for radiologically isolated syndrome and to clarify the concept was also discussed.